1.Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinoma
Yan BIAN ; Ye GAO ; Chaojing LU ; Bo TIAN ; Lei XIN ; Han LIN ; Yanhui ZHANG ; Xun ZHANG ; Siwei ZHOU ; Kangkang WAN ; Jun ZHOU ; Zhaoshen LI ; Hezhong CHEN ; Luowei WANG
Chinese Medical Journal 2024;137(14):1724-1735
Background::Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods::We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results::The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion::The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.
2.Burden of digestive system diseases in China and its provinces during 1990-2019: Results of the 2019 Global Disease Burden Study
Zhiyuan CHENG ; Tinglu WANG ; Yunfei JIAO ; Jinlei QI ; Xun ZHANG ; Siwei ZHOU ; Lei XIN ; Rong WAN ; Maigeng ZHOU ; Zhaoshen LI ; Luowei WANG
Chinese Medical Journal 2024;137(18):2182-2189
Background::Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies. However, comprehensive reports on the burden of digestive system diseases in China are lacking. Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces.Methods::This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence, mortality rate, disability-adjusted life years (DALYs), years of life disability, years of life lost, and changes in the burden of digestive diseases across Chinese provinces from 1990 to 2019. The analysis of disease burden primarily examines the characteristics of sub-disease distribution, time trends, age distribution, and sex distribution. Additionally, we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index (SDI).Results::In 2019, there were 499.2 million cases of digestive system diseases in China, resulting in 1,557,310 deaths. Stomach cancer, colon and rectal cancer, and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases. Meanwhile, cirrhosis and other chronic liver diseases, gastroesophageal reflux disease, and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases. The risk of gastric cancer sharply increases among men after the age of 40 years, leading to a significant disparity in burden between men and women. As the SDI increased, the DALYs associated with digestive system diseases in China and its provinces showed a downward trend.Conclusion::Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI.
3.Burden of esophageal cancer in China from 1990 to 2021:a comparative analysis with Japan and South Korea
Lin FU ; Tinglu WANG ; Yunfei JIAO ; Luowei WANG
Academic Journal of Naval Medical University 2024;45(12):1478-1486
Objective To analyze the burden and trends of esophageal cancer in China from 1990 to 2021,and compare them with Japan and South Korea.Methods Based on the global burden of disease 2021 database,the incidence,mortality,and disability-adjusted life years(DALYs)of esophageal cancer and the corresponding age-standardized rates in China from 1990 to 2021 were analyzed and descriptively studied according to different ages and genders,and compared with Japan and South Korea.The estimated annual percentage change and relative variation were used to evaluate the trend of the burden of esophageal cancer.Four risk factors,including smoking,alcohol consumption,low-vegetable diet,and chewing tobacco,were included and the proportions of esophageal cancer DALYs and death burden attributable to each risk factor were analyzed.Breakdown analysis method was used to analyze the contribution of population growth,population aging,and epidemiological changes to the incidence of esophageal cancer.The age-period-cohort model was used to analyze the effect trends of age,period,and birth cohort on the incidence of esophageal cancer.Pearson correlation analysis was used to evaluate the correlation between age-standardized DALYs rate and socio-demographic index(SDI).The number of incident cases and age-standardized incidence rate(ASIR)of esophageal cancer in China over the subsequent 20 years were predicted by autoregressive integrated moving average model.Results In 2021,the number of incident cases,number of deaths,and DALYs of esophageal cancer in China were 320 805,296 443 and 6 898 666,respectively,with increases of 54.61%,40.61%,and 17.88%over 1990.In 2021,the ASIR,age-standardized mortality(ASMR),and age-standardized DALYs rate of esophageal cancer in China were 15.04/100 000,14.13/100 000,and 317.18/100 000,respectively,which were higher than those in Japan(6.22/100 000,3.81/100 000,and 84.34/100 000,respectively)and South Korea(3.52/100 000,2.29/100 000,and 50.15/100 000,respectively).The burden of esophageal cancer in males was higher than that in females in the 3 countries.In 2021,smoking and alcohol consumption were the 2 major risk factors for esophageal cancer death in China;the increase in the number of incident cases was mainly caused by population growth and population aging.In addition,the ASIR of esophageal cancer in China increased with age,peaking at 85-89 years old.From 1990 to 2021,SDI was negatively correlated with age-standardized DALYs rate of esophageal cancer in China,Japan,and South Korea.It was predicted that by 2041,the ASIR of esophageal cancer in China would continue to decrease to 9.14/100 000,but the number of incident cases would increase to 398 200.Conclusion The burden of esophageal cancer in China remains substantial.In the future,it will be crucial to strengthen the prevention and control of risk factors such as smoking and alcohol consumption.Additionally,efforts should be made to promote early screening,diagnosis,and treatment,particularly among high-risk populations.
4.Characteristic and trend of global capsule endoscopy research based on bibliometrics
Meijuan HAO ; Ye GAO ; Zhiyuan CHENG ; Lei XIN ; Zhuan LIAO ; Zhaoshen LI ; Luowei WANG
Chinese Journal of Digestive Endoscopy 2024;41(8):647-653
Objective:To quantitatively analyze the primary research characteristics and keywords of international and domestic papers in the field of capsule endoscopy with bibliometric methods, and to illustrate the progression of capsule endoscopy research and offer insights for researchers in this domain.Methods:The Stork and visualized software CiteSpace were used to search and analyze the literature on "capsule endoscopy" in the English database of PubMed and the Chinese database of CNKI from 2002 to 2022.Results:A total of 6 011 English articles were identified in the PubMed database during the specified period. Both the number of publications and their citation frequencies displayed an upward trend on a global and domestic scale. The growth rates of global and domestic English publications were 5% and 15%, respectively, with major contributions coming from the United States, Japan, China, Italy and Germany. Key areas of global research interest included magnetic capsule endoscopy, colon capsule endoscopy, inflammatory bowel disease, small bowel capsule endoscopy, capsule endoscopy images, and obscure gastrointestinal bleeding, etc. A total of 2 027 articles were retrieved in the CNKI database, with top three research institutions including Department of Gastroenterology, Changhai Hospital, Naval Medical University; Department of Gastroenterology, Nanfang Hospital, Southern Medical University; School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University. Emerging research keywords encompassed artificial intelligence, deep learning, and guidelines.Conclusion:The study reveals a gradual increase in global research activities related to capsule endoscopy, with China demonstrating significant international academic influence in this field.
5.Development and validation of an artificial intelligence-assisted esophageal cytological risk prediction model for detecting esophageal precancerous lesions
Huishan JIANG ; Ye GAO ; Han LIN ; Lei XIN ; Wei WANG ; Zhaoshen LI ; Luowei WANG
Chinese Journal of Digestive Endoscopy 2024;41(10):762-767
Objective:Artificial intelligence-assisted esophageal cytology was used to develop and validate a risk prediction model for screening esophageal precancerous lesions.Methods:This study was a secondary analysis of data from the esophageal cancer screening trial (EAST). A total of 17 294 subjects were included who underwent upper gastrointestinal endoscopy and artificial intelligence-assisted esophageal cytology screening at 39 tertiary or secondary hospitals and 5 community service centers in areas with high incidence of esophageal squamous cell carcinoma in China from January 1, 2021 to June 30, 2022. Subjects ( n=14 415) screened in the hospital constituted the hospital opportunistic screening cohort, which served as the training set. An artificial intelligence-assisted esophageal cytological risk prediction model (LightGBM model for short) was developed based on light-gradient boosting machine (LightGBM) machine learning algorithm. Subjects undergoing screening at 5 community health service centers ( n=2 879) constituted a community screening cohort, which served as a validation set. The diagnostic efficacy of LightGBM model for esophageal precancerous lesions in the community screening cohort was evaluated by using pathological results of endoscopic biopsy as the golden standard. Results:The LightGBM model, trained in the opportunistic screening cohort, exhibited an area under the receiver operator characteristic (ROC) curve of 0.93 (95% CI: 0.91-0.95) for detecting precancerous lesions. The cutoff value of the ROC curve was determined as 0.08 based on the maximum Youden index. The sensitivity and specificity of LightGBM model were 91.0% (95% CI: 86.9%-95.1%) and 86.2% (95% CI: 85.7%-86.8%), respectively, when the risk prediction score was >0.08 as the screening criterion for precancerous lesions. The sensitivity, specificity, and accuracy of LightGBM model for precancerous lesions in the community screening cohort were 95.2% (20/21), 87.5% (2 502/2 858), and 87.6% (2 522/2 879), respectively. Conclusion:The artificial intelligence-assisted esophageal cytology risk prediction model showcased remarkable sensitivity and specificity in screening for esophageal precancerous lesions, underscoring its potential for widespread adoption and application in esophageal cancer screening.
6.Application of esophageal sponge cytology to esophageal carcinoma screening in high-incidence districts
Shu HUANG ; Ye GAO ; Yadong FENG ; Hailang ZHOU ; Wei WANG ; Xiuyan HAN ; Fazhen XU ; Aijun ZHOU ; Luowei WANG
Chinese Journal of Digestive Endoscopy 2024;41(10):768-773
Objective:To investigate the safety, feasibility and accuracy of esophageal sponge cytology in esophageal carcinoma screening in high-incidence districts.Methods:Opportunistic screening for esophageal carcinoma was conducted on individuals aged 40-75 years with high-risk factors for esophageal carcinoma and visited out-patient clinic in Lianshui People's Hospital from May 2021 to June 2022. A new esophageal cell collector independently developed in China was used for esophageal sponge cytology sampling followed by cytopathological analysis. Atypical squamous cells or more severe lesions were defined as positive esophageal sponge cytology. Then gastroscopy was performed, and all suspicious areas under the endoscopy were biopsied for histopathological examination. Gastroscopy, biopsy histopathology and esophageal sponge cytology were conducted blindly in pairs. Outcome measures included adverse reactions during sampling, subject tolerability (using a visual simulation score), sampling quality, and diagnostic efficacy of esophageal sponge cytology using gastroscopy plus biopsy histopathology as the gold standard.Results:A total of 1 590 patients completed the screening program. During esophageal sponge cytology sampling, no serious adverse events were observed, and the adverse reactions were mainly manifested as vomiting during sampling [0.31% (5/1 590)] and sore throat after sampling [2.45% (39/1 590)], all of which resolved spontaneously without further medical intervention. The majority of subjects [98.62% (1 568/1 590)] reported good tolerance during the procedure. After sampling, 1 526 (95.97%) subjects had completely expanded sponge material, meeting the standard of good sampling quality. The scanning analysis of the digital pathology system showed that the number of sampled cells in 1 590 subjects ranged (2.01-4.00)×10 6, with a median of 3.48×10 6 cells, which could meet the requirements for interpreting cytological results. Using the positive esophageal sponge cytology for the diagnosis of esophageal carcinoma including high-grade intraepithelial neoplasia, esophageal squamous cell carcinoma and adenocarcinoma of esophagogastric junction, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 98.57% (69/70), 91.51% (1 391/1 520), 34.85% (69/198), 99.93% (1 391/1 392), and 91.82% (1 460/1 590), respectively. Conclusion:Esophageal sponge cytology presents promising diagnostic efficacy for esophageal carcinoma screening, offering a simple, safe, convenient, and effective approach in high-incidence esophageal carcinoma regions.
7.Key points in pancreatic cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up (2023)
Zheran CHEN ; Lei XIN ; Luowei WANG
Journal of Clinical Hepatology 2023;39(12):2804-2808
In September 2023, the European Society for Medical Oncology published Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up in Annals of Oncology. The guideline provides recommendations on the epidemiology, diagnosis, and treatment of pancreatic cancer (PC). The guideline highlights the high-risk populations of PC and recommended screening methods, clarifies the diagnostic process of PC and various radiological and molecular biology tests, and mentions the appropriate treatment methods for different types of PC. This article makes an excerpt of this guideline and introduces related recommendations for the clinical treatment of PC, in order to provide a reference for clinical practice.
8.Application of endoclip- and submucosal injection-assisted cannulation technique to difficult cannulation during endoscopic retrograde cholangiopancreatography (with video)
Wei WANG ; Bowei LIU ; Lei XIN ; Luowei WANG ; Zhendong JIN ; Zhaoshen LI
Chinese Journal of Digestive Endoscopy 2023;40(9):697-701
Objective:To evaluate the value of endoclip-assisted and submucosal injection-assisted cannulation techniques for difficult cannulation during endoscopic retrograde cholangiopancreatography (ERCP).Methods:Data of 12 458 patients treated with ERCP for the first time in the First Affilated Hospital of Naval Medical University from June 2015 to September 2020 were retrospectively analyzed. Twenty eight (0.22%) were identified as difficult cannulation where metal clip- or submucosal injection-assisted cannulation was used. The selective cannulation success rate, intubation time and complication incidence of the two techniques in difficult cannulation patients were analyzed.Results:Difficult cannulation was performed in 18 males (64.3%) and 10 females (35.7%) with an age of 69.6±14.1 years assisted by metal clips or submucosal injection. Five cases (17.9%) were type Ⅱ, 5 cases (17.9%) type Ⅲ, and 18 cases (64.3%) type Ⅴ according to papilla classification. Sixteen patients (57.1%) received metal clip-assisted cannulation, and 12 cases (42.9%) submucosal injection-assisted cannulation. Twenty-five (89.3%) patients successfully underwent selective cannulation with the cannulation time of 9.9±4.3 min. One case (3.6%) of mild post-ERCP pancreatitis and 3 cases (10.7%) of post-ERCP hyperamylasemia occurred. No postoperative bleeding or perforation occurred. All patients were cured and discharged after conservative treatment.Conclusion:When selective cannulation is difficult due to poor papilla exposure or deflection, endoclip- or submucosal injection-assisted cannulation can effectively improve the successful selective cannulation rate during ERCP with low complication incidence, which is worth of clinical promotion.
9.Application of air sterilization station to air quality control of digestive endoscopy center
Ye GAO ; Tianjiao WANG ; Luowei WANG ; Han LIN ; Zhaoshen LI
Chinese Journal of Digestive Endoscopy 2023;40(12):992-996
Objective:To investigate the effect of air sterilization station on air quality control of digestive endoscopy center through a national multi-center dynamic monitoring research.Methods:This study was conducted jointly with 15 digestive endoscopy centers in different regions of China. Each center selected 2 endoscopy rooms using level 4 and level 3 digestive endoscopy techniques, one with an air sterilization station (the experimental group) and the other without the device (the control group). The concentrations of PM 5 and PM 0.5 in the rooms before and after the use of air sterilization station were detected and compared. Results:The air quality of all research units failed to reach the standard air cleanliness level 8 without using air sterilization station. After using the air sterilization station, the PM 5 concentration and PM 0.5 concentration of the experimental group in each center under dynamic conditions were lower than those of the control group, and the difference was significant ( P<0.05). The PM 5 concentration and PM 0.5 concentration in the experimental group at each center showed a decreasing trend with start-up time, with significant difference at different start-up times ( P<0.05). The PM 5 concentration could reach the air cleanliness level 8 standard 15.7 minutes after the air sterilization station started, and the PM 0.5 concentration could reach the air cleanliness level 8 standard 25.0 minutes after the air sterilization station started. Conclusion:In the dynamic environment of the digestive endoscopy center, the air sterilization station can significantly improve the air quality in the endoscopy rooms, which is worth promoting in endoscopy rooms of medical institutions of all levels.
10.Utilization and quality assessment of digestive endoscopy in China: results from 5-year consecutive nationwide surveys.
Lei XIN ; Ye GAO ; Zhiyuan CHENG ; Tianjiao WANG ; Han LIN ; Yanan PANG ; Chang SUN ; Zengjun FU ; Zhaoshen LI ; Xudong MA ; Luowei WANG
Chinese Medical Journal 2022;135(16):2003-2010
BACKGROUND:
Worldwide, the volume and availability of digestive endoscopy have undergone dramatic development in recent years, with increasing attention on quality assurance. We investigated the utilization and quality of digestive endoscopy in China from 2015 to 2019 and developed a quantitative quality evaluation tool for medical institutions.
METHODS:
We invited all tertiary/secondary hospitals in Chinese mainland to participate in the survey annually. The questionnaires included the personnel, annual volume, and quality indicators of endoscopy. An endoscopy quality index (EQI) was developed based on recorded quality indicators using principal component analysis to determine the relative weight.
RESULTS:
From 2015 to 2019, 806, 1412, 2644, 2468, and 2541 hospitals were respectively enrolled in this study. The average annual volume of endoscopy increased from 12,445 to 16,206 (1.30-fold) and from 2938 to 4255 (1.45-fold) in tertiary and secondary hospitals, respectively. The most obvious growth was observed in diagnostic colonoscopy (1.44-fold for all hospitals after standardization). The proportion of early cancer among all esophageal and gastric cancers during diagnostic esophagogastroduodenoscopy increased from 12.3% (55,210/448,861) to 17.7% (85,429/482,647) and from 11.4% (69,411/608,866) to 16.9% (107,192/634,235), respectively. The adenoma detection rate of diagnostic colonoscopy increased from 14.9% (2,118,123/14,215,592) to 19.3% (3,943,203/20,431,104). The EQI model included 12 quality indicators, incorporating 64.9% (7.792/12) of the total variance into one comprehensive index. According to the EQI measurements, the quality of endoscopy was higher in tertiary hospitals and hospitals in developed areas with higher volume or more endoscopists than that in other hospitals.
CONCLUSIONS
Digestive endoscopy in China has developed considerably in recent years in terms of both volume and quality. The EQI is a promising tool to quantify the quality of endoscopy at different hospitals.
Humans
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Colonoscopy/methods*
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Endoscopy, Gastrointestinal
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Endoscopy, Digestive System/methods*
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Surveys and Questionnaires
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Adenoma
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China

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